Dopa decarboxylase inhibitor compositions

Abstract

Disclosed herein are formulations containing carbidopa and optionally levodopa, arginine, and other components that have reduced levels of impurities and toxins, particularly degradation productions. Also disclosed herein are methods of treatment diseases or conditions relating to a loss of dopamine or dopaminergic neurons using such formulations, methods of making such formulations, and kits that include such formulations.

What is claimed is: 
     
         1 . A pharmaceutically acceptable formulation comprising:
 (i) levodopa, about 0.1% to about 6% by weight carbidopa, about 1% to about 25% by weight of a component selected from the group consisting of arginine, meglumine, and a combination thereof, and at least one o-quinone scavenger; or   (ii) about 8% to about 16% by weight levodopa, about 1% to about 4% by weight carbidopa, about 0.1% to about 40% by weight of a component selected from arginine, meglumine, and a combination thereof, and at least one o-quinone scavenger,   
       wherein the pharmaceutically acceptable formulation has less than about 1 μg/ml of hydrazine, as determined by a gas chromatography-mass spectrometry (GCMS) method. 
     
     
         2 . The formulation of  claim 1  having less than about 0.1 μg/ml of hydrazine, as determined by a GCMS method. 
     
     
         3 . The formulation of  claim 1  having about 0.1 to about 0.5 μg/ml of hydrazine. 
     
     
         4 . The formulation of  claim 1 , wherein said o-quinone scavenger is selected from the group consisting of ascorbic acid or a salt thereof, L-cysteine, N-acetylcysteine (NAC), glutathione, diacetylcystine and/or a salt thereof, and a combination thereof. 
     
     
         5 . The formulation of  claim 1 , further comprising:
 about 0.1% to about 10% by weight ascorbic acid or a salt thereof, and   a component selected from the group consisting of about 0.01% to about 1% by weight of NAC, about 0.01% to about 1% by weight L-cysteine, about 0.001% to about 1% by weight glutathione, and about 0.001% to about 1% by weight diacetylcystine or a salt thereof.   
     
     
         6 .- 9 . (canceled) 
     
     
         10 . The formulation of  claim 1  comprising about 11% to about 15% by weight levodopa. 
     
     
         11 . (canceled) 
     
     
         12 . A pharmaceutically acceptable formulation comprising:
 (a) carbidopa;   (b) ascorbic acid or a salt thereof; and   (c) one of L-cysteine, NAC, glutathione, and diacetylcystine, or a salt thereof, wherein said formulation has less than about 1 μg/ml of hydrazine, as determined by a GCMS method.   
     
     
         13 . The formulation of  claim 12  having less than about 0.1 μg/ml of hydrazine, as determined by a GCMS method. 
     
     
         14 . (canceled) 
     
     
         15 . The formulation of  claim 12  comprising about 0.1% to 10% by weight ascorbic acid or salt thereof. 
     
     
         16 .- 17 . (canceled) 
     
     
         18 . The formulation of  claim 12 , comprising about 0.01% to about 1% by weight L-cysteine, or a salt thereof. 
     
     
         19 . (canceled) 
     
     
         20 . The formulation of  claim 12  comprising about 0.1% to about 10% by weight carbidopa. 
     
     
         21 .- 26 . (canceled) 
     
     
         27 . The formulation of  claim 12 , further comprising levodopa. 
     
     
         28 . The formulation of  claim 12 , wherein said formulation comprises less than 4% by weight levodopa. 
     
     
         29 .- 31 . (canceled) 
     
     
         32 . The formulation of  claim 12  further comprising arginine, meglumine, or combination thereof. 
     
     
         33 .- 34 . (canceled) 
     
     
         35 . The formulation of  claim 1 , further comprising a surfactant. 
     
     
         36 .- 50 . (canceled) 
     
     
         51 . The formulation of  claim 1 , wherein the pharmaceutically acceptable formulation is a liquid formulation. 
     
     
         52 .- 77 . (canceled) 
     
     
         78 . A method for treating a disease or condition associated with loss of dopamine or dopaminergic neurons in a patient, said method comprising administering to the patient an amount of the pharmaceutically acceptable formulation of  claim 1  in an amount effective to said disease or condition in the patient. 
     
     
         79 . The method of  claim 78  wherein said disease is Parkinson's disease. 
     
     
         80 . The method of  claim 78 , wherein said administration is substantially continuous. 
     
     
         81 . (canceled) 
     
     
         82 . A method of reducing the impurities in a formulation containing levodopa and carbidopa, said method comprising:
 (a) mixing together levodopa and/or carbidopa, and a component selected from L-arginine or meglumine, and antioxidants;   (b) add the mixture of step (a) into pre-heated water or bring the mixture at a temperature and for a time sufficient to dissolve the powders to form a solution;   (c) cooling the solution to room temperature.   
     
     
         83 . The method of  claim 82 , further comprising:
 (d) adding additional water, antioxidants, and/or Tween-80, to the solution of step (c).   
     
     
         84 . The method of  claim 82  wherein the water in step (b) comprises antioxidants prior to said mixing. 
     
     
         85 .- 90 . (canceled)